Prostaglandin E2 (hereinafter referred to as “PGE2”) is known as one of the metabolites in an arachidonic acid cascade. PGE2 exhibits various physiological activities and is involved in a pain inducing and increasing action, a pro-inflammatory action, an anti-inflammatory action, a uterine contractile action, a digestive peristalsis promoting action, an awaking action, a gastric acid secretion inhibiting action, a hypotensive action, a platelet aggregation inhibition action, a bone resorption-promoting action, an angiogenic action, and the like.
There exist four subtypes, EP1, EP2, EP3, and EP4, for PGE2 receptors, which have a wide distribution in various tissues. The activation of the EP1 receptor causes the increase in intracellular Ca2+. The activation of the EP3 receptor causes the increase in intracellular Ca2+ and causes the inhibition of adenylate cyclase, and thus decreases the intracellular cAMP level. The activation of the EP2 and EP4 receptors causes the activation of adenylate cyclase, and thus increases the intracellular cAMP level. In particular, it is believed that the EP4 receptor is related to relaxation of smooth muscles, promotion or inhibition of an inflammatory reaction, lymphocyte differentiation, hypertrophy or proliferation of mesangial cells, secretion of gastrointestinal mucus, and the like (Pharmacology & Therapeutics 2013, 138:485-502; Pharmacological Reviews 2013, 65:1010-1052; and American Journal of Physiology Renal Physiology 2004, 287, F673-F681).
An inhibitor of a PGE2 receptor, that is, an EP receptor antagonist has a binding activity to the EP receptor and inhibits the action by an EP receptor of PGE2. Accordingly, an EP receptor antagonist is expected to be an agent for treating diseases caused by PGE2. Among these, the EP4 receptor antagonist is expected to be a drug for treating EP4-related diseases, for example, renal disease, inflammatory diseases, and various pains, in human and animals (Journal of American Society Nephrology 2010, 21:1678-1690; Proceedings of the National Academy of Sciences, 2010, 107:12233-12238; and The Journal of Pharmacology and Experimental Therapeutics 2008, 325:425-434). In addition, the antagonist selective to the EP4 receptor is preferred from the viewpoint that it can avoid the side-effects based on the antagonism of other EP1, EP2, and EP3 (Physiological Reviews 1999, 79:1193-1226; and Annual Reviews Physiology 2001, 63:579-605).
In Patent Document 1, a compound represented by the following formula (B) is reported as an EP4 receptor antagonist.

(In the formula, the ring D represents a group of the following formula (III), or the like, and in the following formula, the ring D1 represents a monocyclic or bicyclic nitrogen-containing hetero ring which may be substituted with phenyl, R41 represents —X2—B4, X2 represents a C1-6 alkylene or the like, and B4 represents aryl, a hetero ring, or the like, each of which may be substituted with the same or different 1 to 5 groups selected from R4. For the other symbols, refer to this Patent Document.)

In Example 205 of this Patent Document, the following Example compound is disclosed, and this Example compound is disclosed as a specific compound in which the ring D1 is pyrazole.

In Patent Document 2, a compound represented by the following formula (C) is reported as the EP4 receptor antagonist.

(In the formula, R2 represents methyl, fluoromethyl, or the like, and R4 represents fluoromethyl, methoxy, or the like. For the other symbols in the formula, refer to this Patent Document.)
In Patent Document 3, a compound represented by the following formula (D) is reported as an EP4 receptor antagonist.

(In the formula, R2 represents methyl, fluoromethyl (for example, monofluoromethyl, difluoromethyl, and trifluoromethyl), or the like, and R4 represents fluoromethyl, methoxy, or the like. For the other symbols, refer to this Patent Document.)
In Patent Document 4, a compound represented by the following formula (E) is reported as an EP4 receptor ligand.

(For the symbols in the formula, refer to this Patent Document.)
In Patent Document 5, a compound represented by the following formula (F) is reported as an EP4 receptor antagonist.

(In the formula, the ring B and the ring D are the same as or different from each other, and represent aryl which may be substituted or a hetero ring which may be substituted, X represents a single bond, —R00—, or the like, R00 represents lower alkylene, and R1 represents H or the like. A represents a group of the following formula (II), or the like, and in the following formula, Y represents CH or the like, R2 represents R0 or the like, R0 represents lower alkyl, Z represents a single bond or the like, and R3 represents —COOH or the like. For the other symbols, refer to this Patent Document.)

In this Patent Document, there is no disclosure of a specific compound in which the ring D is pyrazole.
In Patent Documents 1 to 5, the structures of the compounds specifically disclosed in Examples are different from that of Compound A.